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Here, we generated a novel replication\u2010defective recombinant adenovirus 40 (rAd40), whose gene delivery properties are totally different from a conventional rAd5. In this study, we have identified intravenous administration with rAd40 expressing mouse mesothelin (Msln) as an effective prophylactic cancer vaccine against metastatic lesions of pancreatic cancer in mice. Intravenous administration of rAd40 (rAd40 i.v.) achieved transgene delivery in wider range of organs compared to rAd5 i.v., while rAd5 was distributed mainly to the liver, spleen, and lungs. Additionally, rAd40 i.v. showed less transduction of the liver or inflammatory responses, resulted in reduced liver toxicity compared to rAd5 i.v. Also, more robust systemic antigen\u2010specific immune responses were stimulated by rAd40 i.v. Pretreatment with a single ovalbumin\u2010expressing rAd40 i.v. prevented tumor growth in mouse subcutaneous models of ovalbumin\u2010expressing pancreatic cancer. When used with Msln\u2010expressing rAd40 i.v., Msln protein expression and metastases were suppressed in a syngeneic orthotopic mouse model of pancreatic cancer, corresponding to the detection of Msln\u2010 and tumor\u2010specific cytotoxic T lymphocyte (CTL). Our novel methods generated antitumor effects against antigen\u2010expressing tumors through antigen\u2010 and tumor\u2010specific CTL\u2010mediated immunity. Thus, our results indicate that a rAd40\u2010based intravenous vaccine provides a new strategy for the effective control of metastatic pancreatic cancer and novel therapy against other cancers and infectious diseases.<\/jats:p>","DOI":"10.1002\/ijc.27983","type":"journal-article","created":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T13:20:27Z","timestamp":1355404827000},"page":"88-97","source":"Crossref","is-referenced-by-count":18,"title":["Intravenous genetic mesothelin vaccine based on human adenovirus 40 inhibits growth and metastasis of pancreatic cancer"],"prefix":"10.1002","volume":"133","author":[{"given":"Satoshi","family":"Yamasaki","sequence":"first","affiliation":[{"name":"Department of Surgery University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Minnesota Minneapolis 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